1. Field of the Invention
The present invention relates generally to the detection and treatment of HSV infection. In particular, the invention relates to polypeptides comprising HSV antigens, DNA encoding HSV antigens, and the use of such compositions for the diagnosis and treatment of HSV infection.
2. Description of the Related Art
The herpes viruses include the herpes simplex viruses (HSV), comprising two closely related variants designated types 1 (HSV-1) and 2 (HSV-2). HSV is a prevalent cause of genital infection in humans, with an estimated annual incidence of 600,000 new cases and with 10 to 20 million individuals experiencing symptomatic chronic recurrent disease. The asymptomatic subclinical infection rate may be even higher. For example, using a type-specific serological assay, 35% of an unselected population of women attending a health maintenance organization clinic in Atlanta had antibodies to HSV type 2 (HSV-2). Although continuous administration of antiviral drugs such as acyclovir ameliorates the severity of acute HSV disease and reduces the frequency and duration of recurrent episodes, such chemotherapeutic intervention does not abort the establishment of latency nor does it alter the status of the latent virus. As a consequence, the recurrent disease pattern is rapidly reestablished upon cessation of drug treatment.
The genome of at least one strain of herpes simplex virus (HSV) has been characterized. It is approximately 150 kb and encodes about 85 known genes, each of which encodes a protein in the range of 50-1000 amino acids in length. Unknown, however, are the immunogenic portions, particularly immunogenic epitopes, that are capable of eliciting an effective T cell immune response to viral infection.
Thus, it is a matter of great medical and scientific need to identify immunogenic portions, preferably epitopes, of HSV polypeptides that are capable of eliciting an effective immune response to HSV infection. Such information will lead to safer and more effective prophylactic pharmaceutical compositions, e.g., vaccine compositions, to substantially prevent HSV infections, and, where infection has already occurred, therapeutic compositions to combat the disease. The present invention fulfills these and other needs.
The present invention provides compositions and methods for the diagnosis and therapy of HSV infection. In one aspect, the present invention provides polypeptides comprising an immunogenic portion of a HSV antigen, or a variant or biological functional equivalent of such an antigen. Certain preferred portions and other variants are immunogenic, such that the ability of the portion or variant to react with antigen-specific antisera is not substantially diminished. Within certain embodiments, the polypeptide comprises an amino acid sequence encoded by a polynucleotide sequence selected from the group consisting of (a) a sequence of any one of SEQ ID NO: 1, 4, 8-9, 13, 16, 19 24, 35-38, 48-49, 52-53, 65-73, 76-89, 98-117, 118-119, 141, 144-152, 179-180 182-183, 184-194 206-210, 213-214, 217-226, 240, 242, 244-247, and 251-252; (b) a complement of said sequence; and (c) sequences that hybridize to a sequence of (a) or (b) under moderately stringent conditions. In specific embodiments, the polypeptides of the present invention comprise at least a portion, preferably at least an immunogenic portion, of a HSV protein that comprises some or all of an amino acid sequence recited in any one of SEQ ID NO: 2, 3, 5, 6, 7, 10-12, 14-15, 17-18, 20-23, 25-33, 39-47, 50-51, 54-64, 74-75, 90-97, 120-121, 122-140, 142-143, 153-178, 181, 195-205 211-212, 215-216, 227-239, 241, 243, 248-250, and 253-254 including variants and biological functional equivalents thereof.
The present invention further provides polynucleotides that encode a polypeptide as described above, or a portion thereof (such as a portion encoding at least 15 contiguous amino acid residues of a HSV protein), expression vectors comprising such polynucleotides and host cells transformed or transfected with such expression vectors.
In a related aspect, polynucleotide sequences encoding the above polypeptides, recombinant expression vectors comprising one or more of these polynucleotide sequences and host cells transformed or transfected with such expression vectors are also provided.
In another aspect, the present invention provides fusion proteins comprising one or more HSV polypeptides, for example in combination with a physiologically acceptable carrier or immunostimulant for use as pharmaceutical compositions and vaccines thereof.
The present invention further provides pharmaceutical compositions that comprise: (a) an antibody, either polyclonal and monoclonal, or antigen-binding fragment thereof that specifically binds to a HSV protein; and (b) a physiologically acceptable carrier.
Within other aspects, the present invention provides pharmaceutical compositions that comprise one or more HSV polypeptides or portions thereof disclosed herein, or a polynucleotide molecule encoding such a polypeptide, and a physiologically acceptable carrier. The invention also provides vaccines for prophylactic and therapeutic purposes comprising one or more of the disclosed polypeptides and an immunostimulant, as defined herein, as well as vaccines comprising one or more polynucleotide sequences encoding such polypeptides and an immunostimulant.
In yet another aspect, methods are provided for inducing protective immunity in a patient, comprising administering to a patient an effective amount of one or more of the above pharmaceutical compositions or vaccines. Any of the polypeptides identified for use in the treatment of patients can be used in conjunction with pharmaceutical agents used to treat herpes infections, such as, but not limited to, Zovirax(copyright) (Acyclovir), Valtrex(copyright) (Valacyclovir), and Famvir(copyright) (Famcyclovir).
In yet a further aspect, there are provided methods for treating, substantially preventing or otherwise ameliorating the effects of an HSV infection in a patient, the methods comprising obtaining peripheral blood mononuclear cells (PBMC) from the patient, incubating the PBMC with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated T cells and administering the incubated T cells to the patient. The present invention additionally provides methods for the treatment of HSV infection that comprise incubating antigen presenting cells with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated antigen presenting cells and administering the incubated antigen presenting cells to the patient. Proliferated cells may, but need not, be cloned prior to administration to the patient. In certain embodiments, the antigen presenting cells are selected from the group consisting of dendritic cells, macrophages, monocytes, B-cells, and fibroblasts. Compositions for the treatment of HSV infection comprising T cells or antigen presenting cells that have been incubated with a polypeptide or polynucleotide of the present invention are also provided. Within related aspects, vaccines are provided that comprise: (a) an antigen presenting cell that expresses a polypeptide as described above and (b) an immunostimulant.
The present invention further provides, within other aspects, methods for removing HSV-infected cells from a biological sample, comprising contacting a biological sample with T cells that specifically react with a HSV protein, wherein the step of contacting is performed under conditions and for a time sufficient to permit the removal of cells expressing the protein from the sample.
Within related aspects, methods are provided for inhibiting the development of HSV infection in a patient, comprising administering to a patient a biological sample treated as described above. In further aspects of the subject invention, methods and diagnostic kits are provided for detecting HSV infection in a patient. In one embodiment, the method comprises: (a) contacting a biological sample with at least one of the polypeptides or fusion proteins disclosed herein; and (b) detecting in the sample the presence of binding agents that bind to the polypeptide or fusion protein, thereby detecting HSV infection in the biological sample. Suitable biological samples include whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid and urine. In one embodiment, the diagnostic kits comprise one or more of the polypeptides or fusion proteins disclosed herein in combination with a detection reagent. In yet another embodiment, the diagnostic kits comprise either a monoclonal antibody or a polyclonal antibody that binds with a polypeptide of the present invention.
The present invention also provides methods for detecting HSV infection comprising: (a) obtaining a biological sample from a patient; (b) contacting the sample with at least two oligonucleotide primers in a polymerase chain reaction, at least one of the oligonucleotide primers being specific for a polynucleotide sequence disclosed herein; and (c) detecting in the sample a polynucleotide sequence that amplifies in the presence of the oligonucleotide primers. In one embodiment, the oligonucleotide primer comprises at about 10 contiguous nucleotides of a polynucleotide sequence peptide disclosed herein, or of a sequence that hybridizes thereto.
In a further aspect, the present invention provides a method for detecting HSV infection in a patient comprising: (a) obtaining a biological sample from the patient; (b) contacting the sample with an oligonucleotide probe specific for a polynucleotide sequence disclosed herein; and (c) detecting in the sample a polynucleotide sequence that hybridizes to the oligonucleotide probe. In one embodiment, the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a polynucleotide sequence disclosed herein, or a sequence that hybridizes thereto.
These and other aspects of the present invention will become apparent upon reference to the following detailed description. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.
SEQ ID NO: 1 sets forth a polynucleotide sequence of an isolated clone designated HSV2I_UL39fragH12A12;
SEQ ID NO: 2 sets forth an amino acid sequence, designated H12A12orf1.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 1;
SEQ ID NO: 3 sets forth the amino acid sequence of the full length HSV-2 UL39 protein;
SEQ ID NO: 4 sets forth a polynucleotide sequence of an isolated clone designated HSV2II_US8AfragD6.B_B11_T7Trc.seq;
SEQ ID NO: 5 sets forth an amino acid sequence, designated D6Borf1.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 4;
SEQ ID NO: 6 sets forth an amino acid sequence, designated D6Borf2.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 4;
SEQ ID NO: 7 sets forth the amino acid sequence of the full length HSV-2 US8A protein;
SEQ ID NO: 8 sets forth a polynucleotide sequence of an isolated clone designated HSV2II_US4fragF10B3_T7Trc.seq;
SEQ ID NO: 9 sets forth a polynucleotide sequence of an isolated clone designated HSV2II_US3fragF10B3_T7P.seq;
SEQ ID NO: 10 sets forth an amino acid sequence, designated F10B3orf2.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 8;
SEQ ID NO: 11 sets forth an amino acid sequence, designated 8F10B3orf1.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 9;
SEQ ID NO: 12 sets forth the amino acid sequence of the full length HSV-2 US3 protein;
SEQ ID NO: 13 sets forth a polynucleotide sequence of an isolated clone designated HSV2II_UL46fragF11F5_T7Trc.seq SEQ ID NO: 14 sets forth an amino acid sequence, designated F11F5orf1.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 13;
SEQ ID NO: 15 sets forth the amino acid sequence of the full length HSV-2 UL46 protein;
SEQ ID NO: 16 sets forth a polynucleotide sequence of an isolated clone designated HSV2II_UL27fragH2C7_T7Trc.seq
SEQ ID NO: 17 sets forth an amino acid sequence, designated H2C7orf1.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 16;
SEQ ID NO: 18 sets forth the amino acid sequence of the full length HSV-2 UL27 protein;
SEQ ID NO: 19 sets forth a polynucleotide sequence of an isolated clone designated HSV2II_UL18fragF10A1_rc.seq;
SEQ ID NO: 20 sets forth an amino acid sequence, designated F10A1 orf3.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 19;
SEQ ID NO: 21 sets forth an amino acid sequence, designated F10A1orf2.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 19;
SEQ ID NO: 22 sets forth an amino acid sequence, designated F10A1orf1.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 19;
SEQ ID NO: 23 sets forth the amino acid sequence of the full length HSV-2 UL18 protein;
SEQ ID NO: 24 sets forth a polynucleotide sequence of an isolated clone designated HSV2II_UL15fragF10A12_rc.seq;
SEQ ID NO: 25 sets forth an amino acid sequence, designated F10A12orf1.pro, of an open reading frame encoded within the polynucleotide of SEQ ID NO: 24;
SEQ ID NO: 26 sets forth the amino acid sequence of the full length HSV-2 UL15 protein;
SEQ ID NO:27 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL46 gene;
SEQ ID NO:28 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL46 gene;
SEQ ID NO:29 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL46 gene;
SEQ ID NO:30 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL46 gene;
SEQ ID NO:31 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL46 gene;
SEQ ID NO:32 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL18 gene;
SEQ ID NO:33 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL18 gene;
SEQ ID NO:34 sets forth a nucleotide sequence of an isolated clone designated RL2_E9A4xe2x80x945_consensus.seq;
SEQ ID NO:35 sets forth the nucleotide sequence of the full length HSV-2 RL2 gene;
SEQ ID NO:36 sets for the nucleotide sequence of an isolated clone designated UL23xe2x80x9422_C12A12_consensus.seq;
SEQ ID NO:37 sets forth the nucleotide sequence of the full length HSV-2 UL23 protein;
SEQ ID NO:38 sets forth the nucleotide sequence of the full length HSV-2 UL22 protein;
SEQ ID NO:39 sets forth an amino acid sequence, designated HSV2_UL23, of an open reading frame encoded by the polynucleotide of SEQ ID NO: 37;
SEQ ID NO:40 sets forth an amino acid sequence designated HSV2_UL23 of an open reading frame encoded within the polynucleotides of SEQ ID NO:36;
SEQ ID NO:41 sets forth an amino acid sequence designated HSV2_UL22 of an open reading frame encoded within the polynucleotides of SEQ ID NO:36;
SEQ ID NO:42 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL23 gene;
SEQ ID NO:43 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL23 gene;
SEQ ID NO:44 sets forth the amino acid sequence of a 15-mer polypeptide derived from an immunogenic portion of the HSVII UL23 gene;
SEQ ID NO:45 sets forth an amino acid sequence, designated HSV2_UL22, of an open reading frame encoded by the polynucleotide of SEQ ID NO:38;
SEQ ID NO:46 sets forth an amino acid sequence, designated RL2_E9A4xe2x80x945_consensus.seq, of an open reading frame encoded by the polynucleotide of SEQ ID NO:34;
SEQ ID NO:47 sets forth an amino acid sequence, designated HSV2_RL2, of an open reading frame encoded by the polynucleotide of SEQ ID NO:35;
SEQ ID NO:48 sets forth a nucleotide sequence of an isolated clone designated G10_UL37consensus.seq;
SEQ ID NO:49 sets forth the nucleotide sequence of the full length HSV-2 UL37 gene;
SEQ ID NO:50 sets forth an amino acid sequence, designated HSV2_UL37, of an open reading frame encoded by the polynucleotide of SEQ ID NO:48; and
SEQ ID NO:51 sets forth an amino acid sequence, designated HSV2_UL37, of an open reading frame encoded by the polynucleotide of SEQ ID NO:49;
SEQ ID NO:52 sets forth the DNA sequence derived from the insert of clone UL46fragF11F5;
SEQ ID NO:53 sets forth the DNA sequence derived from the insert of clone G10;
SEQ ID NO:54 sets forth the amino acid sequence derived from the insert of clone UL46fragF11F5;
SEQ ID NO:55 sets forth the amino acid sequence derived from the insert of clone G10;
SEQ ID NO:56 is amino acid sequence of peptide #23 (amino acids 688-702) of the HSV-2 gene UL15;
SEQ ID NO:57 is amino acid sequence of peptide #30 (amino acids 716-730) of the HSV-2 gene UL15;
SEQ ID NO:58 is amino acid sequence of peptide #7 (amino acids 265-279) of the HSV-2 gene UL23;
SEQ ID NO:59 is amino acid sequence of peptide #2 (amino acids 621-635) of the HSV-2 gene UL46;
SEQ ID NO:60 is amino acid sequence of peptide #8 (amino acids 645-659) of the HSV-2 gene UL46;
SEQ ID NO:61 is amino acid sequence of peptide #9 (amino acids 649-663) of the HSV-2 gene UL46;
SEQ ID NO:62 is amino acid sequence of peptide #11 (amino acids 657-671) of the HSV-2 gene UL46;
SEQ ID NO:63 is amino acid sequence of peptide #33 (amino acids 262-276) of the HSV-2 gene US3;
SEQ ID NO:64 is amino acid sequence of peptide #5 (amino acids 99-113) of the HSV-2 gene US8A.
SEQ ID NO:65 sets forth the polynucleotide sequence of the full length HSV-2 UL39 protein.
SEQ ID NO:66 sets forth the partial polynucleotide sequence of UL39 derived from the HSV2-III library, pools 1F4, 1G2, and 3G11 which were recognized by clone 39.
SEQ ID NO:67 sets forth the partial polynucleotide sequence of UL39 derived from the HSV2-III library, pool 2C4 which was recognized by clone 39.
SEQ ID NO:68 sets forth the 5xe2x80x2 end of the partial polynucleotide sequence of ICP0 derived from the HSV2-III library, pools 3H6, 3F12, and 4B2 which were recognized by clone 47.
SEQ ID NO:69 sets forth the 3xe2x80x2 end of the partial polynucleotide sequence of ICP0 derived from the HSV2-III library, pools 3H6, 3F12, and 4B2 which were recognized by clone 47.
SEQ ID NO:70 sets forth the 5xe2x80x2 end of the partial polynucleotide sequence of ICP0 derived from the HSV2-III library, pool 3A1 which was recognized by clone 47.
SEQ ID NO:71 sets forth the 3xe2x80x2 end of the partial polynucleotide sequence of ICP0 derived from the HSV2-III library, pool 3A1 which was recognized by clone 47.
SEQ ID NO:72 sets forth the 5xe2x80x2 end of the partial polynucleotide sequence of ICP0 derived from the HSV2-III library, pool 2B2 which was recognized by clone 47.
SEQ ID NO:73 sets forth the 3xe2x80x2 end of the partial polynucleotide sequence of ICP0 derived from the HSV2-III library, pool 2B2 which was recognized by clone 47.
SEQ ID NO:74 sets forth the partial amino acid sequence of UL39 derived from the HSV2-III library, pools 1F4, 1G2, and 3G11 which were recognized by clone 39.
SEQ ID NO:75 sets forth the partial amino acid sequence of UL39 derived from the HSV2-III library, pool 2C4 which was recognized by clone 39.
SEQ ID NO:76 sets forth a full length DNA sequence for the HSV-2 gene UL19.
SEQ ID NO:77 sets forth a DNA sequence for the vaccinia virus shuttle plasmid, pSC11.
SEQ ID NO:78 sets forth a full length DNA sequence for the HSV-2 gene, UL47.
SEQ ID NO:79 sets forth a full length DNA sequence for the HSV-2 gene, UL50.
SEQ ID NO:80 sets forth a DNA sequence for the human Ubiquitin gene.
SEQ ID NO:81 sets forth a full length DNA sequence for the HSV-2 gene, UL49.
SEQ ID NO:82 sets forth a DNA sequence corresponding to the coding region of the HSV gene, UL50.
SEQ ID NO:83 sets forth a DNA sequence corresponding to the coding region of the HSV gene, UL49.
SEQ ID NO:84 sets forth a DNA sequence corresponding to the coding region of the HSV gene, UL19.
SEQ ID NO:85 sets forth a DNA sequence corresponding to the coding region of the HSV gene, UL21.
SEQ ID NO:86 sets forth a DNA sequence corresponding to the coding region of the HSV-2 UL47 gene with the Trx2 fusion sequence.
SEQ ID NO:87 sets forth a DNA sequence corresponding to the coding region of the HSV gene, UL47.
SEQ ID NO:88 sets forth a DNA sequence corresponding to the coding region of the HSV gene, UL47 C fragment.
SEQ ID NO:89 sets forth a DNA sequence corresponding to the coding region of the HSV gene, UL39.
SEQ ID NO:90 sets forth an amino acid sequence corresponding to the UL39 protein with a His tag.
SEQ ID NO:91 sets forth an amino acid sequence corresponding to the UL21 protein with a His tag.
SEQ ID NO:92 sets forth an amino acid sequence corresponding to the UL47 protein fused with the Trx and 2 histadine tags.
SEQ ID NO:93 sets forth an amino acid sequence corresponding to the UL47 C fragment with a His tag.
SEQ ID NO:94 sets forth an amino acid sequence corresponding to the UL47 protein with a His tag.
SEQ ID NO:95 sets forth an amino acid sequence corresponding to the UL19 protein with a His tag.
SEQ ID NO:96 sets forth an amino acid sequence corresponding to the UL50 protein with a His tag.
SEQ ID NO:97 sets forth an amino acid sequence corresponding to the UL49 protein with a His tag.
SEQ ID NO:98 sets forth the primer sequence for the sense primer PDM-602, used in the amplification of UL21.
SEQ ID NO:99 sets forth the primer sequence for the reverse primer PDM-603, used in the amplification of UL21.
SEQ ID NO:100 sets forth the primer sequence for the sense primer PDM-466, used in the amplification of UL39.
SEQ ID NO:101 sets forth the primer sequence for the reverse primer PDM-467, used in the amplification of UL39.
SEQ ID NO:102 sets forth the primer sequence for the sense primer PDM-714, used in the amplification of UL49.
SEQ ID NO:103 sets forth the primer sequence for the reverse primer PDM-715, used in the amplification of UL49.
SEQ ID NO:104 sets forth the primer sequence for the sense primer PDM-458, used in the amplification of UL50.
SEQ ID NO:105 sets forth the primer sequence for the reverse primer PDM-459, used in the amplification of UL50.
SEQ ID NO:106 sets forth the primer sequence for the sense primer PDM-453, used in the amplification of UL19.
SEQ ID NO:107 sets forth the primer sequence for the reverse primer PDM-457, used in the amplification of UL19.
SEQ ID NO:108 sets forth the primer sequence for the sense primer PDM-631, used in the amplification of UL47.
SEQ ID NO:109 sets forth the primer sequence for the reverse primer PDM-632, used in the amplification of UL47.
SEQ ID NO:110 sets forth the primer sequence for the sense primer PDM-631, used in the amplification of UL47 A.
SEQ ID NO:111 sets forth the primer sequence for the reverse primer PDM-645, used in the amplification of UL47 A.
SEQ ID NO:112 sets forth the primer sequence for the sense primer PDM-646, used in the amplification of UL47 B.
SEQ ID NO:113 sets forth the primer sequence for the reverse primer PDM-632, used in the amplification of UL47 B.
SEQ ID NO:114 sets forth the primer sequence for the sense primer PDM-631, used in the amplification of UL47 C.
SEQ ID NO:115 sets forth the primer sequence for the reverse primer PDM-739, used in the amplification of UL47 C.
SEQ ID NO:116 sets forth the primer sequence for the sense primer PDM-740, used in the amplification of UL47 D.
SEQ ID NO:117 sets forth the primer sequence for the reverse primer PDM-632, used in the amplification of UL47 D.
SEQ ID NO:118 sets forth a novel DNA sequence for the HSV-2 gene, US8.
SEQ ID NO:119 sets forth the published DNA sequence for the HSV-2 gene, US8, derived from the HG52 strain of HSV-2.
SEQ ID NO:120 sets forth an amino acid sequence encoded by SEQ ID NO:118.
SEQ ID NO:121 sets forth an amino acid sequence encoded by SEQ ID NO:119.
SEQ ID NO:122 sets forth the sequence of peptide 85 (p85), a CD8+ peptide derived from the HSV-2 gene, UL47.
SEQ ID NO:123 sets forth the sequence of peptide 89 (p89), a CD8+ peptide derived from the HSV-2 gene, UL47.
SEQ ID NO:124 sets forth the sequence of peptide 98/99 (p98/99), a CD8+ peptide derived from the HSV-2 gene, UL47.
SEQ ID NO:125 sets forth the sequence of peptide 105 (p105), a CD8+ peptide derived from the HSV-2 gene, UL47.
SEQ ID NO:126 sets forth the sequence of peptide 112 (p112), a CD8+ peptide derived from the HSV-2 gene, UL47.
SEQ ID NO:127 sets forth the sequence of peptide #23 (amino acids 688-702) from the HSV-2 protein UL15.
SEQ ID NO:128 sets forth the sequence of peptide #30 (amino acids 716-730) from the HSV-2 protein UL15.
SEQ ID NO:129 sets forth the sequence of peptide #7 (amino acids 265-272) from the HSV-2 protein UL23.
SEQ ID NO:130 sets forth the sequence of peptide #2 (amino acids 621-635) from the HSV-2 protein UL46.
SEQ ID NO:131 sets forth the sequence of peptide #8 (amino acids 645-659) from the HSV-2 protein UL46.
SEQ ID NO:132 sets forth the sequence of peptide #9 (amino acids 649-663) from the HSV-2 protein UL46.
SEQ ID NO:133 sets forth the sequence of peptide #11 (amino acids 657-671) from the HSV-2 protein UL46.
SEQ ID NO:134 sets forth the sequence of peptide #86 (amino acids 341-355) from the HSV-2 protein UL47.
SEQ ID NO:135 sets forth the sequence of peptide #6 (amino acids 21-35) from the HSV-2 protein UL49.
SEQ ID NO:136 sets forth the sequence of peptide #12 (amino acids 45-59) from the HSV-2 protein UL49.
SEQ ID NO:137 sets forth the sequence of peptide #13 (amino acids 49-63) from the HSV-2 protein UL49.
SEQ ID NO:138 sets forth the sequence of peptide #49 (amino acids 193-208) from the HSV-2 protein UL49.
SEQ ID NO:139 sets forth the sequence of peptide #33 (amino acids 262-276) from the HSV-2 protein US3.
SEQ ID NO:140 sets forth the sequence of peptide #5 (amino acids 99-113) from the HSV-2 protein US8A.
SEQ ID NO:141 sets forth a full length insert DNA sequence corresponding to the clone F10B3.
SEQ ID NO:142 sets forth a full length insert amino acid sequence corresponding to the clone F10B3.
SEQ ID NO:143 sets forth an amino acid sequence for the HSV-2 protein, US4.
SEQ ID NO:144 sets forth a DNA sequence for the HSV-2 protein, UL21.
SEQ ID NO:145 sets forth a DNA sequence for the HSV-2 protein, UL50.
SEQ ID NO:146 sets forth a DNA sequence for the HSV-2 protein, US3.
SEQ ID NO:147 sets forth a DNA sequence for the HSV-2 protein, UL54.
SEQ ID NO:148 sets forth a DNA sequence for the HSV-2 protein, US8.
SEQ ID NO:149 sets forth a DNA sequence for the HSV-2 protein, UL19.
SEQ ID NO:150 sets forth a DNA sequence for the HSV-2 protein, UL46.
SEQ ID NO:151 sets forth a DNA sequence for the HSV-2 protein, UL18.
SEQ ID NO:152 sets forth a DNA sequence for the HSV-2 protein, RL2.
SEQ ID NO:153 sets forth an amino sequence for the HSV-2 protein, UL50.
SEQ ID NO:154 sets forth an amino acid sequence for the HSV-2 protein, UL21.
SEQ ID NO:155 sets forth an amino acid sequence for the HSV-2 protein, US3.
SEQ ID NO:156 sets forth an amino acid sequence for the HSV-2 protein, UL54.
SEQ ID NO:157 sets forth an amino acid sequence for the HSV-2 protein, US8.
SEQ ID NO:158 sets forth an amino acid sequence for the HSV-2 protein, UL19.
SEQ ID NO:159 sets forth an amino acid sequence for the HSV-2 protein, UL46.
SEQ ID NO:160 sets forth an amino acid sequence for the HSV-2 protein, UL18.
SEQ ID NO:161 sets forth an amino acid sequence for the HSV-2 protein, RL2.
SEQ ID NO:162 sets forth the sequence of peptide #43 (amino acids 211-225) from the HSV-2 protein RL2.
SEQ ID NO:163 sets forth the sequence of peptide #41 (amino acids 201-215) from the HSV-2 protein UL46.
SEQ ID NO:164 sets forth the sequence of peptide #50 (amino acids 246-260) from the HSV-2 protein UL46.
SEQ ID NO:165 sets forth the sequence of peptide #51 (amino acids 251-265) from the HSV-2 protein UL46.
SEQ ID NO:166 sets forth the sequence of peptide #60 (amino acids 296-310) from the HSV-2 protein UL46.
SEQ ID NO:167 sets forth the sequence of peptide #74 (amino acids 366-380) from the HSV-2 protein US8.
SEQ ID NO:168 sets forth the sequence of peptide #102 (amino acids 506-520) from the HSV-2 protein UL19.
SEQ ID NO:169 sets forth the sequence of peptide #103 (amino acids 511-525) from the HSV-2 protein UL19.
SEQ ID NO:170 sets forth the sequence of peptide #74 (amino acids 366-380) from the HSV-2 protein UL19.
SEQ ID NO:171 sets forth the sequence of peptide #75 (amino acids 371-385) from the HSV-2 protein UL19.
SEQ ID NO:172 sets forth the sequence of peptide #17 (amino acids 65-79) from the HSV-2 protein UL18.
SEQ ID NO:173 sets forth the sequence of peptide #18 (amino acids 69-83) from the HSV-2 protein UL18.
SEQ ID NO:174 sets forth the sequence of peptide #16 (amino acids 76-90) from the HSV-2 protein UL50.
SEQ ID NO:175 sets forth the sequence of peptide #23 (amino acids 111-125) from the HSV-2 protein UL50.
SEQ ID NO:176 sets forth the sequence of peptide #49 (amino acids 241-255) from the HSV-2 protein UL50.
SEQ ID NO:177 sets forth the sequence of a 9-mer peptide for ICP0(amino acids 215-223).
SEQ ID NO:178 sets forth the sequence of a 10-mer peptide for UL46 (amino acids 251-260).
SEQ ID NO:179 sets forth a DNA sequence of US4 derived from the HG52 strain of HSV-2.
SEQ ID NO:180 sets forth a DNA sequence for the UL47 F coding region.
SEQ ID NO:181 sets forth an amino acid sequence for the UL47 F coding region.
SEQ ID NO:182 sets forth the sequence for primer CBH-002 used in the amplification of UL47 F.
SEQ ID NO:183 sets forth the sequence for primer PDM-632 used in the amplification of UL47 F.
SEQ ID NO:184 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL18.
SEQ ID NO:185 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, LAT-ORF-1.
SEQ ID NO:186 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL48.
SEQ ID NO:187 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL41.
SEQ ID NO:188 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL39.
SEQ ID NO:189 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL37.
SEQ ID NO:190 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL36.
SEQ ID NO:191 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL29.
SEQ ID NO:192 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL25.
SEQ ID NO:193 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, ICP4.
SEQ ID NO:194 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, ICP22.
SEQ ID NO:195 sets forth a full length amino acid sequence corresponding to the HSV-2 open reading frame, UL18.
SEQ ID NO:196 sets forth a full length amino acid sequence corresponding to the HSV-2 open reading frame, ICP22.
SEQ ID NO:197 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, ICP4.
SEQ ID NO:198 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, LAT-ORF-1.
SEQ ID NO:199 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL25.
SEQ ID NO:200 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL29.
SEQ ID NO:201 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL36.
SEQ ID NO:202 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL37.
SEQ ID NO:203 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL39.
SEQ ID NO:204 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL41.
SEQ ID NO:205 sets forth a full length DNA sequence corresponding to the HSV-2 open reading frame, UL48.
SEQ ID NO:206 sets forth the DNA sequence from the E. coli expression cloning library inserts 1/F3 and 1/A7.
SEQ ID NO:207 sets forth the DNA sequence from the E. coli expression cloning library insert 1/H6.
SEQ ID NO:208 sets forth the DNA sequence from the E. coli expression cloning library insert 3/C1.
SEQ ID NO:209 sets forth the DNA sequence common to the inserts 1/F3, 1/A7, 1/H6, and 3/C1.
SEQ ID NO:210 sets forth a full length DNA sequence for the UL19 gene derived from HSV-2 strain HG52.
SEQ ID NO:211 sets forth the amino acid sequence encoded by SEQ ID NO:209.
SEQ ID NO:212 sets forth a full length amino acid sequence for the UL19 gene derived from the HSV-2 strain HG52.
SEQ ID NO:213 sets forth the full length DNA sequence for the US8 gene derived from the clinical isolate RW1874.
SEQ ID NO:214 sets forth the full length DNA sequence for the US8 gene derived from the clinical isolate HV5101.
SEQ ID NO:215 sets forth the full length amino acid sequence for the US8 gene derived from the clinical isolate RW1874.
SEQ ID NO:216 sets forth the full length amino acid sequence for the US8 gene derived from the clinical isolate HV5101.
SEQ ID NO:217 sets forth the DNA sequence corresponding to the insert from clone HH6 D6_B6.
SEQ ID NO:218 sets forth a DNA sequence for the UL21 gene derived from the HSV-2 strain HG52.
SEQ ID NO:219 sets forth a DNA sequence corresponding to the first insert of clone HH20 C12_E1.
SEQ ID NO:220 sets forth a DNA sequence corresponding to the second insert of clone HH20 C12_E1.
SEQ ID NO:221 sets forth a DNA sequence for the UL29 gene derived from the HSV-2 strain HG52.
SEQ ID NO:222 sets forth the DNA sequence corresponding to the insert from clone HH22 F7_A7.
SEQ ID NO:223 sets forth the DNA sequence corresponding to the insert from clone HH22 4/E8_C8.
SEQ ID NO:224 sets forth a DNA sequence for the UL46 gene derived from the HSV-2 strain HG52.
SEQ ID NO:225 sets forth a DNA sequence corresponding to the insert from the clone HH24 G6_H11.
SEQ ID NO:226 sets forth a DNA sequence for the UL47 gene derived from the HSV-2 strain HG52.
SEQ ID NO:227 sets forth a protein sequence encoded by the insert from clone HH6 (D6B6:SEQ ID NO:217).
SEQ ID NO:228 sets forth a full length amino acid sequence for UL21 derived from the HG52 strain of HSV-2.
SEQ ID NO:229 sets forth an amino acid sequence of the UL21 T cell epitope spanning amino acids 281 to 300.
SEQ ID NO:230 sets forth an amino acid sequence encoded by the insert 1C12_E1, from clone HH20.
SEQ ID NO:231 sets forth an amino acid sequence encoded by the insert 2E9_D11, from clone HH20 .
SEQ ID NO:232 sets forth a full-length amino acid sequence for the HSV-2, strain HG52 protein, UL29.
SEQ ID NO:233 sets forth an amino acid sequence from insert F7_A1, clone HH22.
SEQ ID NO:234 sets forth an amino acid sequence from insert 4/E8_C8, clone HH22.
SEQ ID NO:235 sets forth a full-length amino acid sequence for the UL46 protein derived from the HG52 strain of HSV-2.
SEQ ID NO:236 sets forth an amino acid sequence of the reactive T cell epitope derived from UL46, spanning amino acids 621 to 649.
SEQ ID NO:237 sets forth an amino acid sequence encoded by the insert derived from clone HH24 G6_H11.
SEQ ID NO:238 sets forth a full-length amino acid sequence for the HSV-2 gene UL47.
SEQ ID NO:239 sets forth an amino acid sequence of the reactive T cell epitope derived from UL47 spanning amino acids 137-155.
SEQ ID NO:240 sets forth a DNA sequence corresponding to the clone insert TM13 and TM58 F5_G1.
SEQ ID NO:241 sets forth an amino acid sequence encoded by the clone insert TM13 and TM58 F5_G1.
SEQ ID NO:242 sets forth a full length DNA sequence corresponding to the HSV-2 gene, UL54.
SEQ ID NO:243 sets forth a full length amino acid sequence corresponding to UL54 (ICP27) derived from the HG52 strain of HSV-2.
SEQ ID NO:244 sets forth a DNA sequence corresponding to the insert TM39, H11_C3.
SEQ ID NO:245 sets forth a full length DNA sequence corresponding to UL21, derived from the HSV-2 strain, HG52.
SEQ ID NO:246 sets forth a full length DNA sequence corresponding to UL22, derived from the HSV-2 strain, HG52.
SEQ ID NO:247 sets forth a full length DNA sequence corresponding to UL36, derived from the HSV-2 strain, HG52.
SEQ ID NO:248 sets forth a full length amino acid sequence corresponding to UL21 derived from the HG52 strain of HSV-2.
SEQ ID NO:249 sets forth a full length amino acid sequence corresponding to UL22 derived from the HG52 strain of HSV-2.
SEQ ID NO:250 sets forth a full length amino acid sequence corresponding to UL36 derived from the HG52 strain of HSV-2.
SEQ ID NO:251 sets forth a DNA sequence corresponding to the insert of TM51, F7_A8.
SEQ ID NO:252 sets forth a full length DNA sequence corresponding to US4, derived from the HSV-2 strain, HG52.
SEQ ID NO:253 sets forth an amino acid sequence corresponding to clone TM51F7_A8.
SEQ ID NO:254 sets forth a full length amino acid sequence corresponding to US4 derived from the HG52 strain of HSV-2.